KERA_HUMAN
ID KERA_HUMAN Reviewed; 352 AA.
AC O60938;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Keratocan;
DE Short=KTN;
DE AltName: Full=Keratan sulfate proteoglycan keratocan;
DE Flags: Precursor;
GN Name=KERA; Synonyms=SLRR2B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10565548; DOI=10.3109/10425179909033939;
RA Tasheva E.S., Funderburgh J.L., Funderburgh M.L., Corpuz L.M., Conrad G.W.;
RT "Structure and sequence of the gene encoding human keratocan.";
RL DNA Seq. 10:67-74(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND VARIANT CNA2
RP SER-247.
RX PubMed=10802664; DOI=10.1038/75664;
RA Pellegata N.S., Dieguez-Lucena J.L., Joensuu T., Lau S., Montgomery K.T.,
RA Krahe R., Kivelae T., Kucherlapati R., Forsius H., de la Chapelle A.;
RT "Mutations in KERA, encoding keratocan, cause cornea plana.";
RL Nat. Genet. 25:91-95(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Duodenum;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP TISSUE SPECIFICITY, AND UP-REGULATION IN KERATOCONUS CORNEAS.
RX PubMed=11683372; DOI=10.1007/bf03401852;
RA Wentz-Hunter K., Cheng E.L., Ueda J., Sugar J., Yue B.Y.J.T.;
RT "Keratocan expression is increased in the stroma of keratoconus corneas.";
RL Mol. Med. 7:470-477(2001).
RN [5]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-298.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [6]
RP VARIANT CNA2 LYS-215, AND FUNCTION.
RX PubMed=11726611;
RA Lehmann O.J., El-ashry M.F., Ebenezer N.D., Ocaka L., Francis P.J.,
RA Wilkie S.E., Patel R.J., Ficker L., Jordan T., Khaw P.T.,
RA Bhattacharya S.S.;
RT "A novel keratocan mutation causing autosomal recessive cornea plana.";
RL Invest. Ophthalmol. Vis. Sci. 42:3118-3122(2001).
CC -!- FUNCTION: May be important in developing and maintaining corneal
CC transparency and for the structure of the stromal matrix.
CC {ECO:0000305|PubMed:10802664, ECO:0000305|PubMed:11726611}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Cornea (at protein level) (PubMed:10802664,
CC PubMed:11683372). Increased expression in the stroma of keratoconus
CC corneas (PubMed:11683372). Also detected in trachea, and in low levels,
CC in intestine, skeletal muscle, ovary, lung and putamen
CC (PubMed:10802664). {ECO:0000269|PubMed:10802664,
CC ECO:0000269|PubMed:11683372}.
CC -!- PTM: Binds keratan sulfate chains. {ECO:0000250}.
CC -!- DISEASE: Cornea plana 2, autosomal recessive (CNA2) [MIM:217300]: A
CC severe form of cornea plana, a rare ocular disorder characterized by
CC flattened corneal curvature leading to a decrease in refraction,
CC reduced visual activity, hyperopia, hazy corneal limbus, opacities in
CC the corneal parenchyma, and marked arcus senilis often detected at an
CC early age. CNA2 patients manifest extreme hyperopia and additional
CC ocular anomalies such as malformations of the iris, a slit-like pupil,
CC and adhesions between iris and cornea. {ECO:0000269|PubMed:10802664,
CC ECO:0000269|PubMed:11726611}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the small leucine-rich proteoglycan (SLRP)
CC family. SLRP class II subfamily. {ECO:0000305}.
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DR EMBL; AF065988; AAC17741.1; -; Genomic_DNA.
DR EMBL; AF063301; AAC16390.1; -; mRNA.
DR EMBL; AF205403; AAF69126.1; -; mRNA.
DR EMBL; BC032667; AAH32667.1; -; mRNA.
DR CCDS; CCDS9037.1; -.
DR RefSeq; NP_008966.1; NM_007035.3.
DR AlphaFoldDB; O60938; -.
DR SMR; O60938; -.
DR BioGRID; 116264; 26.
DR IntAct; O60938; 15.
DR MINT; O60938; -.
DR STRING; 9606.ENSP00000266719; -.
DR GlyConnect; 1432; 2 N-Linked glycans (1 site).
DR GlyGen; O60938; 4 sites, 2 N-linked glycans (1 site).
DR iPTMnet; O60938; -.
DR PhosphoSitePlus; O60938; -.
DR BioMuta; KERA; -.
DR jPOST; O60938; -.
DR MassIVE; O60938; -.
DR PaxDb; O60938; -.
DR PeptideAtlas; O60938; -.
DR PRIDE; O60938; -.
DR ProteomicsDB; 49681; -.
DR Antibodypedia; 30000; 143 antibodies from 24 providers.
DR DNASU; 11081; -.
DR Ensembl; ENST00000266719.4; ENSP00000266719.3; ENSG00000139330.6.
DR GeneID; 11081; -.
DR KEGG; hsa:11081; -.
DR MANE-Select; ENST00000266719.4; ENSP00000266719.3; NM_007035.4; NP_008966.1.
DR UCSC; uc001tbl.4; human.
DR CTD; 11081; -.
DR DisGeNET; 11081; -.
DR GeneCards; KERA; -.
DR HGNC; HGNC:6309; KERA.
DR HPA; ENSG00000139330; Not detected.
DR MalaCards; KERA; -.
DR MIM; 217300; phenotype.
DR MIM; 603288; gene.
DR neXtProt; NX_O60938; -.
DR OpenTargets; ENSG00000139330; -.
DR Orphanet; 53691; Congenital cornea plana.
DR PharmGKB; PA30088; -.
DR VEuPathDB; HostDB:ENSG00000139330; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000158968; -.
DR HOGENOM; CLU_000288_186_4_1; -.
DR InParanoid; O60938; -.
DR OMA; MECFCPP; -.
DR OrthoDB; 826997at2759; -.
DR PhylomeDB; O60938; -.
DR TreeFam; TF334562; -.
DR PathwayCommons; O60938; -.
DR Reactome; R-HSA-2022854; Keratan sulfate biosynthesis.
DR Reactome; R-HSA-2022857; Keratan sulfate degradation.
DR Reactome; R-HSA-3656225; Defective CHST6 causes MCDC1.
DR Reactome; R-HSA-3656243; Defective ST3GAL3 causes MCT12 and EIEE15.
DR Reactome; R-HSA-3656244; Defective B4GALT1 causes B4GALT1-CDG (CDG-2d).
DR SignaLink; O60938; -.
DR BioGRID-ORCS; 11081; 23 hits in 1062 CRISPR screens.
DR GeneWiki; Keratocan; -.
DR GenomeRNAi; 11081; -.
DR Pharos; O60938; Tbio.
DR PRO; PR:O60938; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; O60938; protein.
DR Bgee; ENSG00000139330; Expressed in calcaneal tendon and 67 other tissues.
DR Genevisible; O60938; HS.
DR GO; GO:0031012; C:extracellular matrix; NAS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0061303; P:cornea development in camera-type eye; IEA:Ensembl.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR Gene3D; 3.80.10.10; -; 2.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR000372; LRRNT.
DR Pfam; PF13516; LRR_6; 1.
DR Pfam; PF13855; LRR_8; 2.
DR SMART; SM00369; LRR_TYP; 6.
DR SMART; SM00013; LRRNT; 1.
DR PROSITE; PS51450; LRR; 11.
PE 1: Evidence at protein level;
KW Disease variant; Disulfide bond; Extracellular matrix; Glycoprotein;
KW Leucine-rich repeat; Proteoglycan; Reference proteome; Repeat; Secreted;
KW Sensory transduction; Signal; Vision.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..352
FT /note="Keratocan"
FT /id="PRO_0000032748"
FT DOMAIN 33..71
FT /note="LRRNT"
FT REPEAT 72..93
FT /note="LRR 1"
FT REPEAT 96..117
FT /note="LRR 2"
FT REPEAT 122..142
FT /note="LRR 3"
FT REPEAT 143..164
FT /note="LRR 4"
FT REPEAT 167..180
FT /note="LRR 5"
FT REPEAT 193..213
FT /note="LRR 6"
FT REPEAT 214..235
FT /note="LRR 7"
FT REPEAT 238..258
FT /note="LRR 8"
FT REPEAT 263..282
FT /note="LRR 9"
FT REPEAT 283..304
FT /note="LRR 10"
FT CARBOHYD 93
FT /note="N-linked (GlcNAc...) (keratan sulfate) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) (keratan sulfate) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 222
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 298
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT DISULFID 42..48
FT /evidence="ECO:0000250|UniProtKB:P21793"
FT DISULFID 46..58
FT /evidence="ECO:0000250|UniProtKB:P21793"
FT DISULFID 303..343
FT /evidence="ECO:0000250|UniProtKB:P21793"
FT VARIANT 215
FT /note="T -> K (in CNA2; dbSNP:rs121917862)"
FT /evidence="ECO:0000269|PubMed:11726611"
FT /id="VAR_012753"
FT VARIANT 235
FT /note="V -> G (in dbSNP:rs737111)"
FT /id="VAR_013564"
FT VARIANT 247
FT /note="N -> S (in CNA2; dbSNP:rs121917858)"
FT /evidence="ECO:0000269|PubMed:10802664"
FT /id="VAR_012754"
SQ SEQUENCE 352 AA; 40509 MW; 0CF8DEC938852D28 CRC64;
MAGTICFIMW VLFITDTVWS RSVRQVYEVH DSDDWTIHDF ECPMECFCPP SFPTALYCEN
RGLKEIPAIP SRIWYLYLQN NLIETIPEKP FENATQLRWI NLNKNKITNY GIEKGALSQL
KKLLFLFLED NELEEVPSPL PRSLEQLQLA RNKVSRIPQG TFSNLENLTL LDLQNNKLVD
NAFQRDTFKG LKNLMQLNMA KNALRNMPPR LPANTMQLFL DNNSIEGIPE NYFNVIPKVA
FLRLNHNKLS DEGLPSRGFD VSSILDLQLS HNQLTKVPRI SAHLQHLHLD HNKIKSVNVS
VICPSPSMLP AERDSFSYGP HLRYLRLDGN EIKPPIPMAL MTCFRLLQAV II
